chr11-48121225-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002843.4(PTPRJ):c.575A>G(p.Asn192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,194 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0064 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 12 hom. )
Consequence
PTPRJ
NM_002843.4 missense
NM_002843.4 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: 0.0980
Genes affected
PTPRJ (HGNC:9673): (protein tyrosine phosphatase receptor type J) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004011065).
BP6
?
Variant 11-48121225-A-G is Benign according to our data. Variant chr11-48121225-A-G is described in ClinVar as [Benign]. Clinvar id is 776609.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00639 (973/152360) while in subpopulation AFR AF= 0.0218 (908/41584). AF 95% confidence interval is 0.0207. There are 11 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRJ | NM_002843.4 | c.575A>G | p.Asn192Ser | missense_variant | 4/25 | ENST00000418331.7 | |
PTPRJ | NM_001098503.2 | c.575A>G | p.Asn192Ser | missense_variant | 4/9 | ||
PTPRJ | XM_017018085.2 | c.527A>G | p.Asn176Ser | missense_variant | 4/25 | ||
PTPRJ | XM_047427374.1 | c.917A>G | p.Asn306Ser | missense_variant | 4/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRJ | ENST00000418331.7 | c.575A>G | p.Asn192Ser | missense_variant | 4/25 | 1 | NM_002843.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00638 AC: 971AN: 152242Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00167 AC: 420AN: 251282Hom.: 3 AF XY: 0.00121 AC XY: 164AN XY: 135788
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GnomAD4 exome AF: 0.000703 AC: 1028AN: 1461834Hom.: 12 Cov.: 34 AF XY: 0.000586 AC XY: 426AN XY: 727222
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GnomAD4 genome ? AF: 0.00639 AC: 973AN: 152360Hom.: 11 Cov.: 32 AF XY: 0.00630 AC XY: 469AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;D;D
Polyphen
0.13
.;B;.;.;.
Vest4
MVP
MPC
0.25
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at